SPON1 Is Associated with Amyloid-β and APOE ϵ4-Related Cognitive Decline in Cognitively Normal Adults

Shane Fernandez; Samantha C. Burnham; Lidija Milicic; Greg Savage; Paul Maruff; Madeline Peretti; Hamid R. Sohrabi; Yen Ying Lim; Michael Weinborn; David Ames; Colin L. Masters; Ralph N. Martins; Stephanie Rainey-Smith; Christopher C. Rowe; Olivier Salvado; David Groth; Giuseppe Verdile; Victor L. Villemagne; Tenielle Porter; Simon M. Laws

doi:10.3233/ADR-200246

SPON1 Is Associated with Amyloid-β and APOE ϵ4-Related Cognitive Decline in Cognitively Normal Adults

Shane Fernandez
, Samantha C. Burnham
, Lidija Milicic
, Greg Savage
, Paul Maruff
, Madeline Peretti
, Hamid R. Sohrabi
, Yen Ying Lim
, Michael Weinborn
, David Ames
, Colin L. Masters
, Ralph N. Martins
, Stephanie Rainey-Smith
, Christopher C. Rowe
, Olivier Salvado
, David Groth
, Giuseppe Verdile
, Victor L. Villemagne
, Tenielle Porter
, Simon M. Laws

Psychology

Research output: Contribution to journal › Article › Research › peer-review

7 Citations (Scopus)

Abstract

Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ϵ4 and rs11023139 in individuals with high amyloid-β burden. APOE ϵ4/rs11023139-A carriers declined significantly faster than APOE ϵ4/rs11023139-G-G carriers in measures of global cognition (p=0.011) and verbal episodic memory (p=0.020). Conclusion: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ϵ4 cognitively normal older adults with a high neocortical amyloid-β burden.

Original language	English
Pages (from-to)	111-120
Number of pages	10
Journal	Journal of Alzheimer's Disease Reports
Volume	5
Issue number	1
DOIs	https://doi.org/10.3233/ADR-200246
Publication status	Published - 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Alzheimer's disease
amyloid-β
APOE
cognitive decline
SPON1
Spondin-1

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10.3233/ADR-200246Licence: CC BY-NC

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Fernandez, S., Burnham, S. C., Milicic, L., Savage, G., Maruff, P., Peretti, M., Sohrabi, H. R., Lim, Y. Y., Weinborn, M., Ames, D., Masters, C. L., Martins, R. N., Rainey-Smith, S., Rowe, C. C., Salvado, O., Groth, D., Verdile, G., Villemagne, V. L., Porter, T., & Laws, S. M. (2021). SPON1 Is Associated with Amyloid-β and APOE ϵ4-Related Cognitive Decline in Cognitively Normal Adults. Journal of Alzheimer's Disease Reports, 5(1), 111-120. https://doi.org/10.3233/ADR-200246

@article{32403bd671124319af635b8259832e15,

title = "SPON1 Is Associated with Amyloid-β and APOE ϵ4-Related Cognitive Decline in Cognitively Normal Adults",

abstract = "Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ϵ4 and rs11023139 in individuals with high amyloid-β burden. APOE ϵ4/rs11023139-A carriers declined significantly faster than APOE ϵ4/rs11023139-G-G carriers in measures of global cognition (p=0.011) and verbal episodic memory (p=0.020). Conclusion: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ϵ4 cognitively normal older adults with a high neocortical amyloid-β burden.",

keywords = "Alzheimer's disease, amyloid-β, APOE, cognitive decline, SPON1, Spondin-1",

author = "Shane Fernandez and Burnham, \{Samantha C.\} and Lidija Milicic and Greg Savage and Paul Maruff and Madeline Peretti and Sohrabi, \{Hamid R.\} and Lim, \{Yen Ying\} and Michael Weinborn and David Ames and Masters, \{Colin L.\} and Martins, \{Ralph N.\} and Stephanie Rainey-Smith and Rowe, \{Christopher C.\} and Olivier Salvado and David Groth and Giuseppe Verdile and Villemagne, \{Victor L.\} and Tenielle Porter and Laws, \{Simon M.\}",

year = "2021",

doi = "10.3233/ADR-200246",

language = "English",

volume = "5",

pages = "111--120",

journal = "Journal of Alzheimer's Disease Reports",

issn = "2542-4823",

publisher = "IOS Press",

number = "1",

}

Fernandez, S, Burnham, SC, Milicic, L, Savage, G, Maruff, P, Peretti, M, Sohrabi, HR, Lim, YY, Weinborn, M, Ames, D, Masters, CL, Martins, RN, Rainey-Smith, S, Rowe, CC, Salvado, O, Groth, D, Verdile, G, Villemagne, VL, Porter, T & Laws, SM 2021, 'SPON1 Is Associated with Amyloid-β and APOE ϵ4-Related Cognitive Decline in Cognitively Normal Adults', Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 111-120. https://doi.org/10.3233/ADR-200246

TY - JOUR

T1 - SPON1 Is Associated with Amyloid-β and APOE ϵ4-Related Cognitive Decline in Cognitively Normal Adults

AU - Fernandez, Shane

AU - Burnham, Samantha C.

AU - Milicic, Lidija

AU - Savage, Greg

AU - Maruff, Paul

AU - Peretti, Madeline

AU - Sohrabi, Hamid R.

AU - Lim, Yen Ying

AU - Weinborn, Michael

AU - Ames, David

AU - Masters, Colin L.

AU - Martins, Ralph N.

AU - Rainey-Smith, Stephanie

AU - Rowe, Christopher C.

AU - Salvado, Olivier

AU - Groth, David

AU - Verdile, Giuseppe

AU - Villemagne, Victor L.

AU - Porter, Tenielle

AU - Laws, Simon M.

PY - 2021

Y1 - 2021

N2 - Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ϵ4 and rs11023139 in individuals with high amyloid-β burden. APOE ϵ4/rs11023139-A carriers declined significantly faster than APOE ϵ4/rs11023139-G-G carriers in measures of global cognition (p=0.011) and verbal episodic memory (p=0.020). Conclusion: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ϵ4 cognitively normal older adults with a high neocortical amyloid-β burden.

AB - Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ϵ4 and rs11023139 in individuals with high amyloid-β burden. APOE ϵ4/rs11023139-A carriers declined significantly faster than APOE ϵ4/rs11023139-G-G carriers in measures of global cognition (p=0.011) and verbal episodic memory (p=0.020). Conclusion: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ϵ4 cognitively normal older adults with a high neocortical amyloid-β burden.

KW - Alzheimer's disease

KW - amyloid-β

KW - APOE

KW - cognitive decline

KW - SPON1

KW - Spondin-1

UR - https://www.scopus.com/pages/publications/85105689483

U2 - 10.3233/ADR-200246

DO - 10.3233/ADR-200246

M3 - Article

C2 - 33782664

AN - SCOPUS:85105689483

SN - 2542-4823

VL - 5

SP - 111

EP - 120

JO - Journal of Alzheimer's Disease Reports

JF - Journal of Alzheimer's Disease Reports

IS - 1

ER -

SPON1 Is Associated with Amyloid-β and APOE ϵ4-Related Cognitive Decline in Cognitively Normal Adults

Abstract

UN SDGs

Keywords

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